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      Omega-3 fatty acid addition during pregnancy

      1 , 1 , 2 , 3 , 4 , 1 , 5 , 6
      Cochrane Pregnancy and Childbirth Group
      Cochrane Database of Systematic Reviews
      Wiley

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          Abstract

          Higher intakes of foods containing omega‐3 long‐chain polyunsaturated fatty acids (LCPUFA), such as fish, during pregnancy have been associated with longer gestations and improved perinatal outcomes. This is an update of a review that was first published in 2006. To assess the effects of omega‐3 LCPUFA, as supplements or as dietary additions, during pregnancy on maternal, perinatal, and neonatal outcomes and longer‐term outcomes for mother and child. For this update, we searched Cochrane Pregnancy and Childbirth’s Trials Register, ClinicalTrials.gov , the WHO International Clinical Trials Registry Platform ( ICTRP ) (16 August 2018), and reference lists of retrieved studies. Randomised controlled trials (RCTs) comparing omega‐3 fatty acids (as supplements or as foods, stand‐alone interventions, or with a co‐intervention) during pregnancy with placebo or no omega‐3, and studies or study arms directly comparing omega‐3 LCPUFA doses or types. Trials published in abstract form were eligible for inclusion. Two review authors independently assessed study eligibility, extracted data, assessed risk of bias in trials and assessed quality of evidence for prespecified birth/infant, maternal, child/adult and health service outcomes using the GRADE approach. In this update, we included 70 RCTs (involving 19,927 women at low, mixed or high risk of poor pregnancy outcomes) which compared omega‐3 LCPUFA interventions (supplements and food) compared with placebo or no omega‐3. Overall study‐level risk of bias was mixed, with selection and performance bias mostly at low risk, but there was high risk of attrition bias in some trials. Most trials were conducted in upper‐middle or high‐income countries; and nearly half the trials included women at increased/high risk for factors which might increase the risk of adverse maternal and birth outcomes. Preterm birth < 37 weeks (13.4% versus 11.9%; risk ratio (RR) 0.89, 95% confidence interval (CI) 0.81 to 0.97; 26 RCTs, 10,304 participants; high‐quality evidence) and early preterm birth < 34 weeks (4.6% versus 2.7%; RR 0.58, 95% CI 0.44 to 0.77; 9 RCTs, 5204 participants; high‐quality evidence) were both lower in women who received omega‐3 LCPUFA compared with no omega‐3. Prolonged gestation > 42 weeks was probably increased from 1.6% to 2.6% in women who received omega‐3 LCPUFA compared with no omega‐3 (RR 1.61 95% CI 1.11 to 2.33; 5141 participants; 6 RCTs; moderate‐quality evidence ). For infants, there was a possibly reduced risk of perinatal death (RR 0.75, 95% CI 0.54 to 1.03; 10 RCTs, 7416 participants; moderate‐quality evidence: 62/3715 versus 83/3701 infants) and possibly fewer neonatal care admissions (RR 0.92, 95% CI 0.83 to 1.03; 9 RCTs, 6920 participants; moderate‐quality evidence ‐ 483/3475 infants versus 519/3445 infants). There was a reduced risk of low birthweight (LBW) babies (15.6% versus 14%; RR 0.90, 95% CI 0.82 to 0.99; 15 trials, 8449 participants; high‐quality evidence); but a possible small increase in large‐for‐gestational age (LGA) babies (RR 1.15, 95% CI 0.97 to 1.36; 6 RCTs, 3722 participants; moderate‐quality evidence, for omega‐3 LCPUFA compared with no omega‐3. Little or no difference in small‐for‐gestational age or intrauterine growth restriction (RR 1.01, 95% CI 0.90 to 1.13; 8 RCTs, 6907 participants; moderate‐quality evidence) was seen. For the maternal outcomes , there is insufficient evidence to determine the effects of omega‐3 on induction post‐term (average RR 0.82, 95% CI 0.22 to 2.98; 3 trials, 2900 participants; low‐quality evidence), maternal serious adverse events (RR 1.04, 95% CI 0.40 to 2.72; 2 trials, 2690 participants; low‐quality evidence), maternal admission to intensive care (RR 0.56, 95% CI 0.12 to 2.63; 2 trials, 2458 participants; low‐quality evidence), or postnatal depression (average RR 0.99, 95% CI 0.56 to 1.77; 2 trials, 2431 participants; low‐quality evidence). Mean gestational length was greater in women who received omega‐3 LCPUFA (mean difference (MD) 1.67 days, 95% CI 0.95 to 2.39; 41 trials, 12,517 participants; moderate‐quality evidence), and pre‐eclampsia may possibly be reduced with omega‐3 LCPUFA (RR 0.84, 95% CI 0.69 to 1.01; 20 trials, 8306 participants; low‐quality evidence). For the child/adult outcomes, very few differences between antenatal omega‐3 LCPUFA supplementation and no omega‐3 were observed in cognition, IQ, vision, other neurodevelopment and growth outcomes, language and behaviour (mostly low‐quality to very low‐quality evidence). The effect of omega‐3 LCPUFA on body mass index at 19 years (MD 0, 95% CI ‐0.83 to 0.83; 1 trial, 243 participants; very low‐quality evidence) was uncertain. No data were reported for development of diabetes in the children of study participants. In the overall analysis, preterm birth < 37 weeks and early preterm birth < 34 weeks were reduced in women receiving omega‐3 LCPUFA compared with no omega‐3. There was a possibly reduced risk of perinatal death and of neonatal care admission , a reduced risk of LBW babies; and possibly a small increased risk of LGA babies with omega‐3 LCPUFA. For our GRADE quality assessments, we assessed most of the important perinatal outcomes as high‐quality (e.g. preterm birth) or moderate‐quality evidence (e.g. perinatal death). For the other outcome domains (maternal, child/adult and health service outcomes) GRADE ratings ranged from moderate to very low, with over half rated as low. Reasons for downgrading across the domain were mostly due to design limitations and imprecision. Omega‐3 LCPUFA supplementation during pregnancy is an effective strategy for reducing the incidence of preterm birth, although it probably increases the incidence of post‐term pregnancies. More studies comparing omega‐3 LCPUFA and placebo (to establish causality in relation to preterm birth) are not needed at this stage. A further 23 ongoing trials are still to report on over 5000 women, so no more RCTs are needed that compare omega‐3 LCPUFA against placebo or no intervention. However, further follow‐up of completed trials is needed to assess longer‐term outcomes for mother and child, to improve understanding of metabolic, growth and neurodevelopment pathways in particular, and to establish if, and how, outcomes vary by different types of omega‐3 LCPUFA, timing and doses; or by characteristics of women. What is the issue? Do omega‐3 long chain polyunsaturated fatty acids (LCPUFA) taken during pregnancy ‐ either as supplements or as dietary additions in food (such as some types of fish) ‐ improve health outcomes for babies and their mothers? This is an update of a Cochrane Review that was first published in 2006. Why is this important? Preterm birth (babies born before 37 weeks pregnancy (gestation)) is a leading cause of disability or death in the first five years of life. Fish and fish oil contain omega‐3 LCPUFA (particularly docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA)) and have been associated with longer pregnancies. So it is suggested that additional omega‐3 LCPUFAs in pregnancy may reduce the number of babies born preterm and may improve outcomes for children and mothers. However, many pregnant women do not eat fish very often. Encouraging pregnant women to eat fatty fish (which generally have low toxin levels) or to use omega‐3 LCPUFA supplements may improve children’s and women's health. This is an update of a Cochrane Review that was first published in 2006. What evidence did we find? We searched for evidence in August 2018 and found 70 randomised controlled trials (RCTs; this type of trial provides the most reliable results) (involving 19,927 women). Most trials evaluated a group of women who received omega‐3 LCPUFA and compared them with a group of women who received something that looked like omega‐3 LCPUFA but did not contain it (placebo) or received no omega‐3. The trials were mostly undertaken in upper‐middle or high‐income countries. Some studies included women at increased risk of preterm birth. The quality of the evidence from the included studies ranged from high to very low; this affected the certainty of the findings for different outcomes. We found the incidence of preterm birth (before 37 weeks) and very preterm birth (before 34 weeks) was lower in women who received omega‐3 LCPUFA compared with no additional omega‐3. There were also fewer babies with low birthweight. However, omega‐3 LCPUFA probably increased the incidence of pregnancies continuing beyond 42 weeks, although there was no difference identified in induction of labour for post‐term pregnancies. The risk of the baby dying or being very sick and going to neonatal intensive care may be lower with omega‐3 LCPUFA compared with no omega‐3. We did not see any differences between groups for serious adverse events for mothers or in postnatal depression. Very few differences between the omega‐3 LCPUFA groups and no omega‐3 groups were observed in child development and growth. Eleven trials reported that they had received industry funding. When we omitted these trials from the main outcomes (such as preterm birth and very preterm birth) it made very little, or no difference, to the results. What does this mean? Increasing omega‐3 LCPUFA intake during pregnancy, either through supplements or in foods, may reduce the incidence of preterm birth (before 37 weeks and before 34 weeks) and there may be less chance of having a baby with a low birthweight. Women who take omega‐3 LCPUFA supplements during pregnancy may also be more likely to have longer pregnancies. More studies are underway and their results will be included in a further update of this review. Future studies could consider if and how outcomes may vary in different populations of women, and could test different ways of increasing omega‐3 LCPUFA during pregnancy.

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          Most cited references285

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          Maternal seafood consumption in pregnancy and neurodevelopmental outcomes in childhood (ALSPAC study): an observational cohort study.

          Seafood is the predominant source of omega-3 fatty acids, which are essential for optimum neural development. However, in the USA, women are advised to limit their seafood intake during pregnancy to 340 g per week. We used the Avon Longitudinal Study of Parents and Children (ALSPAC) to assess the possible benefits and hazards to a child's development of different levels of maternal seafood intake during pregnancy. 11,875 pregnant women completed a food frequency questionnaire assessing seafood consumption at 32 weeks' gestation. Multivariable logistic regression models including 28 potential confounders assessing social disadvantage, perinatal, and dietary items were used to compare developmental, behavioural, and cognitive outcomes of the children from age 6 months to 8 years in women consuming none, some (1-340 g per week), and >340 g per week. After adjustment, maternal seafood intake during pregnancy of less than 340 g per week was associated with increased risk of their children being in the lowest quartile for verbal intelligence quotient (IQ) (no seafood consumption, odds ratio [OR] 1.48, 95% CI 1.16-1.90; some, 1.09, 0.92-1.29; overall trend, p=0.004), compared with mothers who consumed more than 340 g per week. Low maternal seafood intake was also associated with increased risk of suboptimum outcomes for prosocial behaviour, fine motor, communication, and social development scores. For each outcome measure, the lower the intake of seafood during pregnancy, the higher the risk of suboptimum developmental outcome. Maternal seafood consumption of less than 340 g per week in pregnancy did not protect children from adverse outcomes; rather, we recorded beneficial effects on child development with maternal seafood intakes of more than 340 g per week, suggesting that advice to limit seafood consumption could actually be detrimental. These results show that risks from the loss of nutrients were greater than the risks of harm from exposure to trace contaminants in 340 g seafood eaten weekly.
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            Effect of DHA supplementation during pregnancy on maternal depression and neurodevelopment of young children: a randomized controlled trial.

            Uncertainty about the benefits of dietary docosahexaenoic acid (DHA) for pregnant women and their children exists, despite international recommendations that pregnant women increase their DHA intakes. To determine whether increasing DHA during the last half of pregnancy will result in fewer women with high levels of depressive symptoms and enhance the neurodevelopmental outcome of their children. A double-blind, multicenter, randomized controlled trial (DHA to Optimize Mother Infant Outcome [DOMInO] trial) in 5 Australian maternity hospitals of 2399 women who were less than 21 weeks' gestation with singleton pregnancies and who were recruited between October 31, 2005, and January 11, 2008. Follow-up of children (n = 726) was completed December 16, 2009. Docosahexaenoic acid-rich fish oil capsules (providing 800 mg/d of DHA) or matched vegetable oil capsules without DHA from study entry to birth. High levels of depressive symptoms in mothers as indicated by a score of more than 12 on the Edinburgh Postnatal Depression Scale at 6 weeks or 6 months postpartum. Cognitive and language development in children as assessed by the Bayley Scales of Infant and Toddler Development, Third Edition, at 18 months. Of 2399 women enrolled, 96.7% completed the trial. The percentage of women with high levels of depressive symptoms during the first 6 months postpartum did not differ between the DHA and control groups (9.67% vs 11.19%; adjusted relative risk, 0.85; 95% confidence interval [CI], 0.70-1.02; P = .09). Mean cognitive composite scores (adjusted mean difference, 0.01; 95% CI, -1.36 to 1.37; P = .99) and mean language composite scores (adjusted mean difference, -1.42; 95% CI, -3.07 to 0.22; P = .09) of children in the DHA group did not differ from children in the control group. The use of DHA-rich fish oil capsules compared with vegetable oil capsules during pregnancy did not result in lower levels of postpartum depression in mothers or improved cognitive and language development in their offspring during early childhood. anzctr.org.au Identifier: ACTRN12605000569606.
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              Fish Oil-Derived Fatty Acids in Pregnancy and Wheeze and Asthma in Offspring.

              Background Reduced intake of n-3 long-chain polyunsaturated fatty acids (LCPUFAs) may be a contributing factor to the increasing prevalence of wheezing disorders. We assessed the effect of supplementation with n-3 LCPUFAs in pregnant women on the risk of persistent wheeze and asthma in their offspring. Methods We randomly assigned 736 pregnant women at 24 weeks of gestation to receive 2.4 g of n-3 LCPUFA (fish oil) or placebo (olive oil) per day. Their children formed the Copenhagen Prospective Studies on Asthma in Childhood2010 (COPSAC2010) cohort and were followed prospectively with extensive clinical phenotyping. Neither the investigators nor the participants were aware of group assignments during follow-up for the first 3 years of the children's lives, after which there was a 2-year follow-up period during which only the investigators were unaware of group assignments. The primary end point was persistent wheeze or asthma, and the secondary end points included lower respiratory tract infections, asthma exacerbations, eczema, and allergic sensitization. Results A total of 695 children were included in the trial, and 95.5% completed the 3-year, double-blind follow-up period. The risk of persistent wheeze or asthma in the treatment group was 16.9%, versus 23.7% in the control group (hazard ratio, 0.69; 95% confidence interval [CI], 0.49 to 0.97; P=0.035), corresponding to a relative reduction of 30.7%. Prespecified subgroup analyses suggested that the effect was strongest in the children of women whose blood levels of eicosapentaenoic acid and docosahexaenoic acid were in the lowest third of the trial population at randomization: 17.5% versus 34.1% (hazard ratio, 0.46; 95% CI, 0.25 to 0.83; P=0.011). Analyses of secondary end points showed that supplementation with n-3 LCPUFA was associated with a reduced risk of infections of the lower respiratory tract (31.7% vs. 39.1%; hazard ratio, 0.75; 95% CI, 0.58 to 0.98; P=0.033), but there was no statistically significant association between supplementation and asthma exacerbations, eczema, or allergic sensitization. Conclusions Supplementation with n-3 LCPUFA in the third trimester of pregnancy reduced the absolute risk of persistent wheeze or asthma and infections of the lower respiratory tract in offspring by approximately 7 percentage points, or one third. (Funded by the Lundbeck Foundation and others; ClinicalTrials.gov number, NCT00798226 .).
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                Author and article information

                Journal
                Cochrane Database of Systematic Reviews
                Wiley
                14651858
                November 15 2018
                Affiliations
                [1 ]Healthy Mothers, Babies and Children, South Australian Health and Medical Research Institute; Women's and Children's Hospital 72 King William Road Adelaide South Australia Australia 5006
                [2 ]The University of Adelaide; School of Psychology; North Terrace, Adelaide Adelaide South Australia Australia 5001
                [3 ]The University of Adelaide; ARCH: Australian Research Centre for Health of Women and Babies, Robinson Research Institute, Discipline of Obstetrics and Gynaecology; Adelaide South Australia Australia 5006
                [4 ]Statens Serum Institut; Centre for Fetal Programming, Department of Epidemiology; Copenhagen Denmark
                [5 ]The University of Adelaide; School of Paediatrics and Reproductive Health; Adelaide Australia Australia
                [6 ]Women's and Children's Health Research Institute; North Adelaide Australia
                Article
                10.1002/14651858.CD003402.pub3
                6516961
                30480773
                86add14c-211f-4272-aef3-fac9dd378f54
                © 2018
                History

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